Positron emission tomography is a unique technique that provides quantitative cross-sectional images of radiotracer concentrations in myocardium and affords non-invasive measurements of regional myocardial blood flow and metabolism. We hypothesize that exercise in patients with coronary artery disease (CAD) not only produces myocardial perfusion abnormalities but also metabolic derangements that can be detected noninvasively with PET and radiotracers of blood flow and metabolism. Our aim is to develop a superior technique for diagnosing the severity, location, and extent of exercise-induced ischemia. The positron-emitter Nitrogen-13 labeled ammonia will be used with PET to measure myocardial blood flow. Fluorine-18 labeled fluorodeoxyglucose (FDG), an analog of glucose, will be used to measure glucose metabolism, and N-13 labeled glutamate (GLU) will be used to assess the metabolism of glutamate. The metabolism of glucose and glutamate are both affected by ischemia. An important part of this proposal is to determine what the normal response of flow and metabolism of glucose and glutamate is to exercise in subjects without cardiac disease. Each subject/patient will have a baseline PET study with N-13 ammonia and either FDG or GLU prior to undergoing a supine exercise test. Repeat imaging with the same two isotopes will be performed sequentially with exercise testing, with the N-13 ammonia imaging being performed first. Observations by PET in CAD patients will be compared to those in age-matched normals to define abnormal responses. The duration of ischemia-induced metabolic abnormalities will be assessed. The PET data will also be correlated with the clinical status of the patient (e.g. severity of angina), ECG changes with exercise, quantitative arteriograms, and global and regional left ventricular function. It is anticipated that the proposed research will improve the detection of CAD and determination of the extent of disease, but more importantly will allow determination of the functional significance of coronary artery disease; e.g. the separation of critical from non-critical stenoses and assessment of the severity of stress-induced ischemia. Lastly, the proposed studies are likely to provide new insights into the pathophysiology of stress-induced ischemia.